Composition and method for preparing biocompatible surfaces

Abstract

The invention provides methods and compositions for providing biocompatible surfaces to medical articles. In particular the invention provides biocompatible coatings with heparin activity. In some aspects, the biocompatible coatings of the invention are able to release a bioactive agent. The coatings can be formed using biostable or biodegradable polymeric material and photoreactive groups. The invention also provides methods for improving the quality of bioactive agent-containing coatings by performing pre-irradiation of biocompatible coating compositions.

1. A medical article having a bioactive agent-releasing coating having heparin activity, the coating comprising:
 (a) a first coated layer comprising a bioactive agent; and 
 (b) a second coated layer formed from a second coating composition comprising heparin, photoreactive groups, and a polymeric material, wherein the second coating composition is irradiated prior to being disposed to form the second coated layer. 
 
     
     
       2. The medical article of  claim 1  wherein the first coated layer comprises a hydrophobic polymer. 
     
     
       3. The medical article of  claim 2  wherein the hydrophobic polymer of the first coated layer is selected from the group of poly(alkyl(meth)acrylates). 
     
     
       4. The medical article of  claim 3  wherein the hydrophobic polymer of the first coated layer is poly(butyl(meth)acrylate). 
     
     
       5. The medical article of  claim 2  wherein the first coated layer further comprises a polymer that is different than, but can be blended with, the hydrophobic polymer. 
     
     
       6. The medical article of  claim 5  wherein the first coated layer further comprises poly(ethylene-co-vinyl acetate). 
     
     
       7. The medical article of  claim 1  wherein the polymeric material of the second coated layer comprises a hydrophobic polymer. 
     
     
       8. The medical article of  claim 7  wherein the hydrophobic polymer of the first coated layer and the hydrophobic polymer of the second coated layer are the same. 
     
     
       9. The medical article of  claim 1  wherein the bioactive agent is selected from the group consisting of anti-proliferative agents, an anti-mitotics, and antibiotics. 
     
     
       10. The medical article of  claim 9  wherein the bioactive agent is selected from rapamycin and analogs thereof. 
     
     
       11. The medical article of  claim 1  wherein the photoreactive groups are pendent from heparin. 
     
     
       12. The medical article of  claim 1  wherein the second coated layer further comprises a component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin. 
     
     
       13. The medical article of  claim 12  wherein the second coated layer comprises polyvinylpyrrolidone. 
     
     
       14. The medical article of  claim 12  wherein photoreactive groups are pendent from a component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin. 
     
     
       15. The medical article of  claim 14  wherein the photoreactive groups are pendent from polyvinylpyrrolidone. 
     
     
       16. The medical article of  claim 15  wherein the photoreactive groups are pendent from both heparin and poly(vinylpyrrolidone). 
     
     
       17. The medical article of  claim 1  being an intraluminal prosthesis. 
     
     
       18. The medical article of  claim 17  being a stent. 
     
     
       19. The medical article of  claim 1  comprising a third coated layer comprising a polymeric material, wherein the third coated layer is either between the first coated layer and the surface, or between the first coated layer and the second coated layer. 
     
     
       20. A method for preparing a medical article having a bioactive agent-releasing coating with heparin activity, comprising the steps of:
 (a) providing a medical article having a first coated layer comprising a bioactive agent; and 
 (b) irradiating a composition comprising heparin, photoreactive groups, and polymeric material to activate the photoreactive groups; 
 (c) after step (b), disposing the irradiated composition on the first coated layer. 
 
     
     
       21. A medical article having a bioactive agent-releasing coating having heparin activity of 10 mU/cm 2  or greater, the coating comprising:
 (a) biostable or biodegradable polymer; 
 (b) bioactive agent; 
 (c) heparin, and 
 (d) photoreactive groups, wherein the photoreactive groups are activated prior to being placed in contact with the medical article. 
 
     
     
       22. A medical article having a bioactive agent-releasing coating comprising:
 (a) hydrophobic polymer 
 (b) bioactive agent; 
 (c) heparin; 
 (d) photoreactive groups; and 
 (e) a component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin.